{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:44:51Z","timestamp":1790095491990,"version":"4.0.1"},"reference-count":152,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T00:00:00Z","timestamp":1649980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100003965","name":"Migraine Research Foundation","doi-asserted-by":"publisher","award":["2019 Migraine Research Foundation Impact Award"],"award-info":[{"award-number":["2019 Migraine Research Foundation Impact Award"]}],"id":[{"id":"10.13039\/100003965","id-type":"DOI","asserted-by":"publisher"}]},{"name":"DPMM program of the UEF","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Migraine is a disabling neurovascular disorder characterized by severe pain with still limited efficient treatments. Endocannabinoids, the endogenous painkillers, emerged, alternative to plant cannabis, as promising analgesics against migraine pain. In this thematic review, we discuss how inhibition of the main endocannabinoid-degrading enzymes, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), could raise the level of endocannabinoids (endoCBs) such as 2-AG and anandamide in order to alleviate migraine pain. We describe here: (i) migraine pain signaling pathways, which could serve as specific targets for antinociception; (ii) a divergent distribution of MAGL and FAAH activities in the key regions of the PNS and CNS implicated in migraine pain signaling; (iii) a complexity of anti-nociceptive effects of endoCBs mediated by cannabinoid receptors and through a direct modulation of ion channels in nociceptive neurons; and (iv) the spectrum of emerging potent MAGL and FAAH inhibitors which efficiently increase endoCBs levels. The specific distribution and homeostasis of endoCBs in the main regions of the nociceptive system and their generation \u2018on demand\u2019, along with recent availability of MAGL and FAAH inhibitors suggest new perspectives for endoCBs-mediated analgesia in migraine pain.<\/jats:p>","DOI":"10.3390\/ijms23084407","type":"journal-article","created":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T04:21:28Z","timestamp":1650255688000},"page":"4407","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Inhibiting Endocannabinoid Hydrolysis as Emerging Analgesic Strategy Targeting a Spectrum of Ion Channels Implicated in Migraine Pain"],"prefix":"10.3390","volume":"23","author":[{"given":"Adriana","family":"Della Pietra","sequence":"first","affiliation":[{"name":"A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1301-9064","authenticated-orcid":false,"given":"Juha","family":"Savinainen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashid","family":"Giniatullin","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/0333102417738202","article-title":"Headache classification committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition","volume":"38","author":"Vincent","year":"2018","journal-title":"Cephalalgia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-540-33823-9_1","article-title":"Peripheral and Central Mechanisms of pain generation","volume":"Volume 177","author":"Schaible","year":"2006","journal-title":"Handbook of Experimental Pharmacology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s11916-017-0629-5","article-title":"Neuropathic Pain: Central vs. Peripheral Mechanisms","volume":"21","author":"Meacham","year":"2017","journal-title":"Curr. 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